The specific objectives of this grant are: 1) To define the acute toxicities of new anticancer agents in patients with advanced cancer; 2) To redefine the acute toxicities and pharmacokinetics of existing anticancer agents administered in combination with colony stimulating factors and other toxicity ameliorating agents such as nerve growth factor and WR-2721, which may facilitate the exploration of more effective doses and schedules; 3) To provide information on the pharmacologic characteristics (absorption, distribution, metabolism, and elimination) of selected antitumor agents; 4) To define treatment regimens for evaluation of antitumor activity in Phase Il trials; 5) Based on pharmacologic characteristics, to establish appropriate Phase Il doses in special patient populations, such as those with impaired end-organ function or with heavy pretreatment, geriatric populations, and to explore pharmacokinetic and pharmacodynamic differences based on gender, race or ethnic group; 6) To obtain preliminary information on pharmacokinetic/ pharmacodynamic correlations which can then be extended in Phase Il trials; and 7) To incorporate ancillary basic laboratory studies, when possible and appropriate, to enhance our understanding of the biochemical and/or biological mechanisms of drug actions. These objectives will be achieved by Phase l and clinical pharmacokinetic studies of new agents; either alone or in combination with existing agents. Such studies may be conceptually considered to have two aspects, clinical evaluation and pharmacological evaluation. Metabolites will be isolated and analyzed using nuclear magnetic resonance and/or mass spectroscopy. Complete pharmacokinetic analysis will be carried out with one or more computer programs. Such studies might also include companion pharmacogenetic genotyping or phenotyping, such as for N-acetylation, glucuronidation or P450-mediated oxidation. All trials will include an exploratory analysis of pharmacokinetic and/or pharmacodynamic differences by gender and race. There will be careful collection of pharmacokinetic data and analysis of the relationship between such pharmacokinetic measurements and effect. In general, the measured effects will be toxicity, but there may be selective trials where analysis of relationships between pharmacokinetics and response are warranted. In addition to providing a preliminary pharmacodynamic model, we will also attempt to develop a limited sampling strategy for subsequent Phase II evaluation.